Technical Field
The present disclosure relates to multilayer implants, and more particularly, multilayer implants suitable for delivering therapeutic agents including a first layer comprising at least one glycosaminoglycan having a first degree of acetylation and a second layer comprising at least one glycosaminoglycan having a degree of acetylation different from the first degree of acetylation.
Background of Related Art
Delivery of a therapeutic agent through the use of implantable medical devices is described in a wide variety of manners. Existing methods of such delivery of a therapeutic agent predominantly focus on the use of water-soluble drugs and polymers to form thin surface coatings positioned on the surface of the medical device which provide limited therapeutic payload and limited control over the release of the therapeutic agent.
In addition, highly water-soluble drugs may be difficult to formulate for controlled or sustained release in that highly water-soluble drugs may either: be susceptible to hydrolysis and quickly released in an aqueous environment thereby being unable to maintain a controlled or sustained release, or, offer limited solubility in the organic systems particularly useful with hydrophobic or water-insoluble drug carriers, i.e., hydrophobic polymers. Limited solubility of the highly water-soluble drugs may further lead to poor encapsulation efficiencies of the drug and limited therapeutic payload on the implantable device. Such hydrophilic drugs need a sufficient water barrier to sustain release. Current systems are challenged from a drug payload and sustained release standpoint including offering therapeutic benefits.
Poly(ethylene glycol) (PEG), a hydrophilic polymer that exhibits acceptable toxicity, and immunogenicity has found great utility in biotechnology, specifically, in forming films, foams and/or hydrogels. PEG is generally considered to be biocompatible and is not immunogenic, which is to say that PEG is generally capable of coexistence with living tissues and does not tend to produce an immune response in the body. However, conventional films, foams, or hydrogels and other medical implants based on PEG and other synthetic biocompatible polymers may be susceptible to in-vivo degradation, generally induced by hydrolysis of specific linkages of the polymer chains (e.g., ester linkages). Thus, such degradation profiles may be considered passive, since degradation primarily occurs due to the presence of water. It would be desirable to provide implants which may include PEG, PEG derivatives, or other synthetic biocompatible polymers that may be suitable for in-vivo enzymatic degradation. It would be beneficial to provide implantable medical devices capable of controlling the release of a therapeutic agent by including tunable or controllable materials via enzymatic degradation and which are not limited by their susceptibility to hydrolysis only.